DESCRIPTION: Chronic rhinosinusitis (CRS) affects over 11 million Americans each year at an annual cost of $8.6 billion. CRS is treated with topical medications and oral antibiotics, but faild response to medical therapy results in 257,000 surgeries annually in the U.S. While surgery alters anatomy, it does not address the inflammatory mediators contributing to this disease. Oral antibiotic and anti-inflammatory medicines are, therefore, needed before and after surgery, but long-term use may not be feasible due to cost and systemic side-effects. Topical medications potentially deliver high concentrations of these drugs to nasal mucosa while minimizing systemic side-effects. However, these potent drugs often fail to help patients even after surgery, possibly due in part to insufficient drug delivery to affected areas. Furthermore, patient instructions for using topical drugs have not been studied in a CRS population, even though this medication is frequently prescribed for this population. The long-term objective of the proposed research is to fundamentally improve CRS treatment by optimizing medical treatment, specifically, maximizing topical drug delivery in areas of the sinonasal cavity affected by CRS. By improving and optimizing medical treatment of CRS, downstream benefits to society and patients can potentially be realized - e.g. refined criteria for patient selection for sinus surger, decreased healthcare related costs, and decreased morbidities related to sinus surgery, and ultimately increased patient well-being and satisfaction. In this project, we will focus on improving the use of nasal sprays, the topical medication most frequently prescribed for CRS. We will combine computational fluid dynamics (CFD) modeling with experiments in nasal replicas and in CRS patients in a prospective clinical study to quantify aerosol particle delivery to target sites in the sinonasal cavities of CRS patients before and after functional endoscopic sinus surgery (FESS), the most frequent surgical treatment for CRS. Our central hypotheses are that (1) there are combinations of head positions, nozzle positions, and breathing techniques that increase target-site particle deposition (TSPD) (optimal use conditions) before and after FESS over TSPD obtained using physician recommendations for these factors (current use conditions), and (2) CFD-derived optimal use conditions will increase TSPD in nasal replicas and in CRS patients compared to TSPD under current use conditions. The proposed research is expected to develop instructions and specifications for improved use of nasal sprays and nebulizers that maximize target-site particle deposition. This information will help improve medical management of CRS, potentially leading to better outcomes for patients who suffer from this prevalent disease. In addition, this research will be the basis for a subsequent randomized, controlled, clinical trial that will measure clinical outcomes in CRS patients after maximal delivery of aerosolized topical medications.